This invention covers the acid addition salt of 9-cyclohexyl-2-propoxy-9H-purine-6-amine with 2-hydroxyethanesulfonic acid (isethionic acid) having an acid to base molecular ratio of 2:1. The compound of this invention is classified in general as a drug, bio-affecting and body-treating type of compound. The base component of the subject salt is referred to herein by code number MJ 13156 and is represented by the following structural formula. ##STR1##
Naito, et al., U.S. Pat. No. 4,172,829 patented Oct. 30, 1979 describes preparation of MJ 13156, its use as a non-adrenergic bronchodilator and conversion to pharmaceutically acceptable acid addition salt by conventional methods. The term "pharmaceutically acceptable acid addition salts" as used therein included those salts formed from mineral acids such hydrochloric, hydrobromic, hydroiodic, nitric, sulfuric, phosphoric, and the like; and also organic acids such as acetic, citric, pivalic, lactic, tartaric, oxalic, succinic, maleic, and the like. The conventional method disclosed for preparing the acid addition salts involved dissolving the free base in an inert solvent, and reacting it with about one equivalent weight of a suitable organic or inorganic acid to produce the desired salt, and recovering the salt by solvent precipitation or lyophilization. These conventional pharmaceutically acceptable acid addition salts of MJ 13156 are not well suited for present use due to limited solubility and, in some cases, lack of stability.
When a substance is employed for medical purposes, it is recognized that solubility of the therapeutic agent often is the controlling factor in determining route of administration and dosage forms. For instance, a water soluble substance can be generally administered intravenously whereas a water insoluble material is limited to other forms of parenteral administration such as intramuscular and subcutaneous routes. Additionally, therapeutic agents having water solubility also facilitate the preparation of various oral and topical dosage forms for human administration. Accordingly, the prime objective of the present invention was to provide a water soluble, stable, therapeutically acceptable form of the bronchodilator agent MJ 13156 which could be administered by several routes, e.g., orally, intravenously, and topically.